Polypharmacy and potential drug-drug interactions for people with HIV in the UK from the Climate-HIV database.

OBJECTIVES: People with HIV (PWHIV) are likely to need therapies for comorbidities as they age. We assessed risk of drug-drug interactions (DDIs) in PWHIV. METHODS: The Climate-HIV electronic recording system was used to cross-sectionally analyse records from PWHIV aged ≥ 18 years attending four UK HIV units with a current antiretroviral (ARV) prescription in February 2018. Antiretroviral and non-ARV medications were categorized by clinical significance of DDIs (University of Liverpool DDI tool). Potential DDIs were predicted using treatment guidelines for commonly recorded comorbidities. RESULTS: Among 4630 PWHIV (44% female), 41% were ≥ 50 years old. The average number of non-ARV comedications increased from < 1 for patients aged ≤ 24 years to > 5 for patients aged ≥ 75 years; 65% were taking one or more non-ARV comedications. The median (interquartile range) number of non-ARVs was 1 (0-2) and 2 (1-5) for those aged < 50 and ≥ 50 years, respectively. Common comorbidities/concurrent health conditions occurred more frequently in patients aged ≥ 50 years vs. < 50 (53% vs. 34%). Boosted protease inhibitors were associated with the highest proportion of contraindicated comedications; dolutegravir and raltegravir had the fewest. For non-ARVs, sildenafil and quetiapine were most likely to result in DDIs. Guideline-recommended treatments for hepatitis C, hepatitis B, and tuberculosis had the highest proportions of contraindications when combined with ARV regimens, while treatments for hepatitis C, malignancy, and mental health conditions had the highest proportion of combinations potentially causing DDIs requiring dose monitoring or adjustment. CONCLUSIONS: Non-ARV use by PWHIV is high and increases with age. Treatment decisions for ageing PWHIV should consider guideline recommendations for comorbidities.

Experiences of stigma and discrimination in social and healthcare settings among trans people living with HIV in the UK.

The People Living with HIV StigmaSurvey UK 2015 was a community led national survey investigating experiences of people living with HIV in the UK in the past 12 months. Participants aged 18 and over were recruited through over 120 cross-sector community organisations and 46 HIV clinics to complete an anonymous online survey. Trans is an umbrella term which refers to individuals whose current gender identity is different to the gender they were assigned at birth. Trans participants self-identified via gender identity and gender at birth questions. Descriptive analyses of reported experiences in social and health care settings were conducted and multivariate logistic regression analyses were used to identify sociodemographic predictors of reporting being treated differently to non-HIV patients, and being delayed or refused healthcare treatment in the past 12 months. 31 out of 1576 participants (2%) identified as trans (19 trans women, 5 trans men, 2 gender queer/non-binary, 5 other). High levels of social stigma were reported for all participants, with trans participants significantly more likely to report worrying about verbal harassment (39% vs. 23%), and exclusion from family gatherings (23% vs. 9%) in the last 12 months, compared to cisgender participants. Furthermore, 10% of trans participants reported physical assault in the last 12 months, compared to 4% of cisgender participants. Identifying as trans was a predictor of reporting being treated differently to non-HIV patients (48% vs. 30%; aOR 2.61, CI 1.06, 6.42) and being delayed or refused healthcare (41% vs. 16%; aOR 4.58, CI 1.83, 11.44). Trans people living with HIV in the UK experience high levels of stigma and discrimination, including within healthcare settings, which is likely to impact upon health outcomes. Trans-specific education and awareness within healthcare settings could help to improve service provision for this demographic.

The people living with HIV stigma survey UK 2015: HIV-related sexual rejection and other experiences of stigma and discrimination among gay and heterosexual men.

We aim to understand the difference in stigma and discrimination, in particular sexual rejection, experienced between gay and heterosexual men living with HIV in the UK. The People Living with HIV StigmaSurvey UK 2015 recruited a convenience sample of persons with HIV through over 120 cross sector community organisations and 46 HIV clinics to complete an online survey. 1162 men completed the survey, 969 (83%) gay men and 193 (17%) heterosexual men, 92% were on antiretroviral therapy. Compared to heterosexual men, gay men were significantly more likely to report worrying about workplace treatment in relation to their HIV (21% vs. 11%), worrying about HIV-related sexual rejection (42% vs 21%), avoiding sex because of their HIV status (37% vs. 23%), and experiencing HIV-related sexual rejection (27% vs. 9%) in the past 12 months. In a multivariate logistic regression controlling for other sociodemographic factors, being gay was a predictor of reporting HIV-related sexual rejection in the past 12 months (aOR 2.17, CI 1.16, 4.02). Both gay and heterosexual men living with HIV experienced stigma and discrimination in the past 12 months, and this was higher for gay men in terms of HIV-related sexual rejection. Due to the high proportion of men reporting sexual rejection, greater awareness and education of the low risk of transmission of HIV among people on effective treatment is needed to reduce stigma and sexual prejudice towards people living with HIV.

Incorporating HIV/hepatitis B virus/hepatitis C virus combined testing into routine blood tests in nine UK Emergency Departments: the "Going Viral" campaign.

OBJECTIVES: Routine HIV screening is recommended in those UK hospitals and primary care settings where the HIV prevalence is > 0.2%. For hepatitis B virus (HBV) and hepatitis C virus (HCV), however, testing is targeted at at-risk groups. We investigated the prevalence of these blood-borne viruses (BBVs) during a routine testing pilot in UK Emergency Departments (EDs). METHODS: During the "Going Viral" campaign (13-19 October 2014), nine UK EDs in areas of high HIV prevalence offered routine tests for HIV, HBV and HCV to adults having blood taken as part of routine care. Patients who tested positive were linked to care. RESULTS: A total of 7807 patients had blood taken during their ED visit; of these, 2118 (27%) were tested for BBVs (range 9-65%). Seventy-one BBV tests were positive (3.4%) with 32 (45.1%) new diagnoses. There were 39 HCV infections (15 newly diagnosed), 17 HIV infections (six newly diagnosed), and 15 HBV infections (11 newly diagnosed). Those aged 25-54 years had the highest prevalence: 2.46% for HCV, 1.36% for HIV and 1.09% for HBV. Assuming the cost per diagnosis is £7, the cost per new case detected would be £988 for HCV, £1351 for HBV and £2478 for HIV. CONCLUSIONS: In the first study in the UK to report prospectively on BBV prevalence in the ED, we identified a high number of new viral hepatitis diagnoses, especially hepatitis C, in addition to the HIV diagnoses. Testing for HIV alone would have missed 54 viral hepatitis diagnoses (26 new), supporting further evaluation of routine BBV testing in UK EDs.

Diagnostic utility of urethral smears in predicting urethral chlamydia in HIV-infected men.

We collected data from 218 HIV-infected men to assess the usefulness of the urethral smear and symptoms in predicting Chlamydia trachomatis infection. Prevalence of urethral chlamydia was 9%. A polymorphonuclear leucocyte (PMNL) count>or=5 was 73% sensitive and 71% specific for C. trachomatis infection. Adjusted odds ratio for risk of chlamydial infection was significant for urethral irritation (7.48; 1.54-36.4), a PMNL count of 20 or more (9.83; 2.52-8.4) and a PMNL count of 5-19 (4.10; 1.34-12.5). We had to perform 50 urethral smears in HIV-positive men without symptoms to treat one case of C. trachomatis at the time of visit. Findings suggest that the presence of symptoms, in particular urethral irritation may be associated with chlamydial urethritis and that the higher the urethral PMNL count, the more likely it is for C. trachomatis to be detected. The findings in this study also lend further support to recent guidelines that urethral microscopy is not useful in asymptomatic men and hence should be abandoned.

Integrated community-based sexual health services for young people in urban areas: are we meeting the needs of the local community?

Community-based sexual health services (SHS) are intended to improve access for people who may have difficulty attending traditional genitourinary medicine clinics. The objective of this study was to review uptake of sexually transmitted infection (STI) testing in an outreach clinic for those under 25 in an area where Black and minority ethnic groups comprise the majority of the local population. A retrospective case-notes review was undertaken of those attending. Standards were that Fraser guidelines should be completed in all under 16-year-old and all clients should be offered STI testing, HIV testing and contraception (if applicable) in accordance with local standards. One hundred and seventeen clients attended. Ten percent self-reported ethnicity was Asian. Thirty-six (31%) clients tested for chlamydia. Thirty (26%) had an HIV test. Five (14% of those tested) had a positive nucleic acid amplification test for chlamydia. Five (13%) of those requesting long term contraception had STI testing. This service has successfully improved access to STI screening. However, there may have been missed opportunities to offer tests in those requesting contraception. Under-representation of those of non-white ethnicity suggests access to SHS may be a particular problem and further work is required to improve the sexual health of the local community.

Changes in the provision of post-exposure prophylaxis for HIV after sexual exposure following introduction of guidelines and publicity campaigns.

In July 2004, British Association of Sexual Health and HIV (BASHH) published guidelines for post-exposure prophylaxis following sexual exposure (PEPSE) and the Terence Higgins Trust (THT) launched a campaign promoting PEPSE among men who have sex with men (MSM). We evaluated subsequent changes in PEPSE attendances. Individuals requesting PEPSE in 2004 were identified from clinic databases. Comparisons of clinical data, exposure characteristics and follow-up were made pre and post campaign. Data were available for 197/216 (91%) PEP attendances. The proportion requesting PEP following sexual exposure increased significantly following the campaign. The majority commencing PEPSE were MSM, with the proportion of MSM increasing significantly from 36/46 (78%) pre to 76/80 (95%) following the campaign. Most prescriptions were in high-risk groups and within guidelines. Times to initiation and completion rates were unchanged. Access to PEPSE following the THT campaign and introduction of BASHH guidelines increased. Promotion of earlier initiation of PEPSE and improvement of completion and follow-up is required.

Age-related serum levels of insulin-like growth factor-I, -II and IGF-binding protein-3 following myocardial infarction.

Aging retards the repair process by decreasing hormone secretion from the somatotrophic axis, which plays a major role in tissue reconstruction after injury. The aim of this study was to determine the effect of aging on serum insulin-like growth factor-I (IGF-I), IGF-II and IGF-binding protein-3 (IGFBP-3) levels following myocardial infarction (MI). For four consecutive days, we monitored the variation of serum IGF-I, IGF-II and IGFBP-3 concentrations in 26 patients aged 19-71 years who were diagnosed with MI. Serum IGF-I, IGF-II and IGFBP-3 were measured daily by double antibody radioimmunoassay. Daily serum IGF-I concentrations showed a significant negative correlation with age (r = -0.528, P< 0.001). Total serum IGF-I was significantly (P = 0.002) higher in the younger age group (patients under 50 years) compared to the older group (50 years and over); 206 +/- 16 ng/ml vs 136 +/- 12 ng/ml. During this investigation, younger patients (under 50 years) showed no significant daily variations in IGF-I levels compared to older patients (50 years and over) who presented a significant decline (P = 0.012). Total serum IGF-II in both groups decreased significantly with time. Total serum IGFBP-3 in the younger age group was significantly higher (P = 0.046) than in the older age group (3.42 +/- 0.18 microgram/ml vs 2.95 +/- 0.13 microgram/ml). MI patients in both groups showed significantly lower IGF-I and IGF-II (IGFs) with higher IGFBP-3 compared to age- and sex-adjusted levels of normal adults (controls). The present results confirm that age and cardiac condition affect IGFs and IGFBP-3 levels. We are inclined to believe that older patients with a cardiac condition are less able to maintain their blood IGF-I levels during the recovery period compared to younger patients. Given the biological impact of IGF-I on regeneration, this could explain why older patients take longer to recover and heal poorly in comparison to younger patients.

Cardiorespiratory and stress hormone responses during first dose surfactant administration in neonates with RDS.

Our hypothesis was that surfactant instilled into the trachea, followed by body positioning maneuvers utilized to enhance drug distribution, could alter hemodynamic function and stimulate the release of catecholamines. We conducted a prospective randomized study designed to compare the immediate physiologic effects of the first dose of Exosurf Neonatal (5 mL/kg; n = 16) or Survanta (4 mL/kg; n = 18), when surfactant administration was standardized with strict adherence to drug company protocol. Physiologic variables were monitored continuously. Arterial blood gases (ABG) and plasma catecholamine concentrations were measured before, and 5 minutes after, surfactant administration. Both surfactants had an immediate effect on arterial oxygen saturation (SaO2), partial pressure of oxygen in arterial blood (PaO2), and oxygen index (OI). The improvement in oxygenation after surfactant therapy was similar in both groups. There was no significant difference in the mean umbilical arterial blood pressure (ABP) following surfactant therapy in both groups. High concentrations of plasma norepinephrine (reflecting activity of the sympathetic nerves) and epinephrine (a measure of secretion from the adrenal medulla) indicate that preterm infants with respiratory distress syndrome (RDS) prior to treatment mount a substantial stress response. The currently recommended techniques for instillation of surfactant appear not to trigger a significant further surge of plasma catecholamines or to acutely change mean ABP. Alternatively, it may be possible that the lack of response was because catecholamine release was already maximal.

Vitamin D deficiency in pregnant women of ethnic minority: a potential contributor to preeclampsia.

OBJECTIVE: We investigated risk for comorbidities and preeclampsia at low vitamin D levels in ethnic minorities. STUDY DESIGN: Umbilical cord vitamin D (25(OH)D) concentration was determined in urban minorities: 80.9% African American and 17% Hispanic mothers-baby pairs. To identify the correlation between vitamin D levels and high-risk comorbidities which result in preeclampsia, multivariate logistic regression analyses were performed. RESULT: Below the Institute of Medicine threshold of 25(OH)D for pregnant women (25 ng ml⁻¹), obesity (P=0.055) and pregestational diabetes (odds ratio (OR)=2.056) were observed. The study median was 16 ng ml⁻¹ (<25th percentile), at which gestational hypertension (P=0.042), chronic hypertension (OR=4.842) and pregestational diabetes (OR=3.45) became relevant. The risk for preeclampsia increased 12-fold with gestational hypertension (P=0.003) and 14-fold with combined chronic and gestational hypertension (P=0.001). CONCLUSION: Pregnant women of ethnic minority had lower median vitamin D levels which may contribute to a potential risk for preeclampsia.

Starting treatment according to guidelines evaluation: a multicentre audit of HIV patients in the UK.

The aim of this audit was to assess whether HIV patients are being started on antiretroviral therapy (ART) according to British and European guidelines. Data were collected from the Survey of Prevalent HIV Infections Diagnosed (SOPHID) return for 2010 at five major HIV management centres in the UK. Data from this 3873 patient cohort revealed 52 patients who should have been receiving ART according to the guidelines but were not. Of these, 23 patients elected not to start ART despite clinical advice to the contrary. Information required to assist in the decision for earlier ART initiation (CD4 count 350­500 cells/mL) was missing for some patients. Clinicians must pay attention to the regular assessment of patients with a CD4 count of 351­500 cells/mL so that all those who may benefit from earlier treatment are identified. Future research should investigate patient barriers to initiating therapy following recommendation by a clinician.

The systematic monitoring of transfusion microbiology test kit performance.

The Transfusion Microbiology Test Systems Monitoring Group (TMTSMG) was established as a National Blood Service (NBS) working group to monitor the performance of the microbiology screening assays used within the NBS Testing Laboratories. The group's primary objective was to ensure that technical performance (especially sensitivity, specificity and wastage) remains consistent with that established during validation. This includes the identification and investigation of significant variation in performance and any untoward incidents. The group is also responsible for optimizing transfusion microbiology working practice across the NBS through nationally agreed standards and procedures. Over the past 9 years, a total of 44 assays from 15 suppliers have been monitored. Five assays have been withdrawn from use as a result of identified poor performance; two hepatitis B virus surface antigen assays owing to poor sensitivity, two syphilis agglutination assays with nonspecific (false) reactive rates sustained above contract limits and one human cytomegalovirus antibody assay that persistently failed the manufacturer's quality control criteria. This approach has enabled the differentiation of genuine kit performance issues from 'natural variation' in kit performance, and local instrumentation or training issues. The NBS has been able to address the issues with suppliers much earlier and resolve minor issues before they became major problems. In addition, a lot release system has been developed and implemented, comprising a formal, centralized initial scientific assessment of each new manufacturer's lot, followed by 'delivery acceptance' testing at each site. This system helps to ensure that the evaluated minimum sensitivity and specificity of the assays is maintained from 'lot to lot'.

Risk of undiagnosed infection in men attending a sexual assault referral centre.

OBJECTIVES: To investigate men undergoing forensic examination at the Haven, a specialist centre for the management of sexual assault in south London. METHODS: Forensic notes of 92 men attending the Haven from May 2000 to August 2003 were identified and a detailed review performed. RESULTS: Males ranged in age from 12 to 51 years, with 83% within the range 12-35 years. 78% were white. Of those who were sexually active (n=82) 30% were heterosexual, 34% were homosexual, and the remainder provided no information regarding sexual orientation. Most clients were referred by the police (n=79) and attended within 3 days of the alleged assault (n=73). Many of the victims had increased vulnerability to assault-for example, through alcohol or drug consumption or mental health difficulties. One assailant was reported in 61 cases but two or more assailants in 26. Women were reported as assailants in four cases. The sexual assault was frequently accompanied by other physical assault (n=45). Use/threat of a weapon was reported in 18 cases. Rape or attempted rape was reported in 59 cases and was the most common assault. Non-genital injuries were documented in 37 men (40%). Anal injuries were seen in 31 (34%). The non-attendance rate at follow up was 41%. Post-exposure prophylaxis (PEP) against HIV was commenced in 31 men (34%). 23 of the 54 men (43%) reporting rape and 14 of the 31 (45%) with anal injuries initiated PEP. CONCLUSIONS: The number of men presenting after sexual assault is likely to increase but despite significant risk many do not engage with medical care. This carries an unknown risk of HIV and other STI transmission.

Mapping of antigenic sites in human neuron-specific enolase by expression subcloning.

Human serum neuron-specific enolase (NSE) is a marker of neurons and of small-cell carcinoma of the lung; improved immunoassays of NSE remain an important goal. Here, we used overlapping complementary DNA (cDNA) clones for reconstruction to express full-length recombinant NSE, and also to express a set of cloned subfragments through the prokaryotic expression vectors pUEX and pUBEX. Subfragments expressed as fusion proteins were used to characterize immunogenic and antigenic regions and epitopes and, expressed as affinity matrices, to derive purified, fractionated polyclonal antibodies. NSE epitope data can be visualized with yeast enolase-1 crystal structure coordinates: The two protein sequences align almost perfectly and are 61% identical. This approach demonstrates the complementarity of cDNA expression with techniques of polyclonal antiserum and monoclonal antibody production and with chemical peptide synthesis in the refinement of immunodiagnostic reagents.

Effects of dexamethasone and triiodothyronine on oligohydramnios-induced pulmonary hypoplasia.

We observed for differential effects of maternal treatment with dexamethasone, triiodothyronine (T3), or both in late gestation on the growth of fetal rat lungs during oligohydramnios-induced pulmonary hypoplasia (PH). Timed-pregnant mothers were randomly selected into four treatment groups: controls (no hormone treatment); dexamethasone only; T3 only; and both dexamethasone and T3. Each underwent amniocentesis of one uterine horn on day 15 of gestation. Untouched littermate on the opposite horn served as internal control. On days 19 and 20, treated mothers were given dexamethasone (0.2 mg/kg) or T3 (7 mg/kg intramuscularly), or both and were delivered on day 21 (term) by hysterotomy. Amniocentesis resulted in PH, defined as decreased wet lung weight to body weight ratio and lung DNA contents, 83% and 90% of control, respectively (P < 0.05). Body weight and lung weight decreased with hormone treatment for both with and without amniocentesis. Although hormone treatment resulted in smaller lungs, there was no significant difference in lung weight to body weight ratio for either group with or without amniocentesis. This suggests that hormone treatment resulted in proportionate growth retardation. All hormone treatments decreased the total lung DNA content during amniocentesis (P < 0.05). Growth suppression of fetal lung associated with maternal hormone treatment is superimposed on the pulmonary hypoplasia induced by oligohydramnios.

Novel plate culture method to improve the microbiological diagnosis of peritonitis in patients on continuous ambulatory peritoneal dialysis.

A novel economical plate culture technique incorporating Tween 80 was used for the isolation of organisms from dialysis effluent in cases of continuous ambulatory peritoneal dialysis peritonitis. It was found to be convenient for routine laboratory use and increased the yield of positive plate cultures in specimens without antibiotics from 53 to 75% (P less than 0.01) and in specimens containing antibiotics from 24 to 38% (P less than 0.05). It allowed for the identification and susceptibility testing of isolates 24 h earlier than did broth culturing and a more ready appreciation of mixed cultures and contaminants.

Chronic administration of growth hormone-releasing factor increases wound strength and collagen maturation in granulation tissue.

The effects of chronic administration of growth hormone-releasing factor (GRF) on wound healing were studied in rats. Cutaneous wound strength was measured by tensometry at 5, 10, and 14 days postwounding in rats implanted with a slow-release pellet which contained a compressed mixture of a fatty acid and [desamino Tyr1, D-Ala2, Ala15]hGRF(1-29)NH2 or the fatty acid alone. There was a significant increase in wound tensile strength in GRF-treated rats compared to controls at each measurement: Day 5, 130 +/- 12 vs 97 +/- 14 g; Day 10, 402 +/- 18 vs 280 +/- 11 g; Day 14, 830 +/- 17 vs 614 +/- 14 g (P less than 0.01 for each value). Granulation tissue obtained from subcutaneously implanted polyvinyl alcohol sponges encased in silicone tubing was also studied. The amount of collagen deposited in the granulation tissue was estimated by measuring the hydroxyproline (Hyp) content of sponges retrieved 5, 10, and 14 days postinsertion from GRF-treated and control rats. Hyp content (nmole/mg sponge) was similar in both treated and control animals at each measurement: Day 5, 1.7 +/- 0.2 vs 2.2 +/- 0.2; Day 10, 31.9 +/- 4.1 vs 26.7 + 0.4; and Day 14, 41.6 +/- 7.3 vs 38.5 +/- 4.4. Hyp/proline, Hyp/glycine, and glycine/total amino acid ratios, evaluated after 10 days, were also similar in both groups. Collagen from the granulation tissue of sponges retrieved after 14 days from treated and control rats was studied by electron microscopy (magnifications, 7,100 and 22,720).(ABSTRACT TRUNCATED AT 250 WORDS)